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揭示 miR-146a 的治疗潜力:靶向动脉粥样硬化中的固有炎症。

Unveiling the therapeutic potential of miR-146a: Targeting innate inflammation in atherosclerosis.

机构信息

King's College London School of Cardiovascular and Metabolic Medicine, London, UK.

Bandung City Regional General Hospital, Bandung, Indonesia.

出版信息

J Cell Mol Med. 2024 Oct;28(19):e70121. doi: 10.1111/jcmm.70121.

Abstract

Atherosclerosis is the foremost vascular disease, precipitating debilitating complications. Although therapeutic strategies have historically focused on reducing cholesterol deposition, recent insights emphasize the pivotal role of inflammation. Innate inflammation significantly contributes to plaque instability and rupture, underscoring the need for intervention across all disease stages. Numerous studies have highlighted the therapeutic potential of targeting innate immune pathways in atherosclerosis, revealing significant advancements in understanding the molecular mechanisms underlying inflammatory processes within arterial lesions. Notably, research has demonstrated that the modulation of microRNA-146a (miR-146a) expression impacts innate inflammation, effectively halts atherosclerosis progression, and enhances plaque stability by targeting interleukin-1 receptor-associated kinase (IRAK) and activating TNF receptor-associated factor 6 (TRAF6), a signalling pathway involving toll-like receptors (TLRs). Understanding the intricate mechanisms involved is crucial. This study provides a comprehensive analysis of the evidence and underlying mechanisms through which miR-146a exerts its effects. Integrating these findings into clinical practice may herald a transformative era in managing atherosclerotic cardiovascular disease.

摘要

动脉粥样硬化是首要的血管疾病,会引发使人衰弱的并发症。虽然治疗策略历史上一直集中在减少胆固醇沉积上,但最近的研究结果强调了炎症的关键作用。先天炎症对斑块不稳定和破裂有重大影响,这突显了在所有疾病阶段都需要进行干预的必要性。许多研究强调了靶向动脉粥样硬化中先天免疫途径的治疗潜力,揭示了对动脉病变中炎症过程的分子机制的深入理解。值得注意的是,研究表明,调节 microRNA-146a (miR-146a) 的表达会影响先天炎症,通过靶向白介素-1 受体相关激酶 (IRAK) 和激活肿瘤坏死因子受体相关因子 6 (TRAF6) ,有效地阻止动脉粥样硬化的进展,并增强斑块的稳定性,这是一个涉及 Toll 样受体 (TLRs) 的信号通路。了解其中涉及的复杂机制至关重要。本研究全面分析了 miR-146a 发挥作用的证据和潜在机制。将这些发现整合到临床实践中可能预示着管理动脉粥样硬化性心血管疾病的新时代的到来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81e/11467738/41f7edb75e6d/JCMM-28-e70121-g001.jpg

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